Skin cancer is the most prevalent cancer in the USA, and melanoma is the most malignant of skin cancers. The incidence of melanoma in the USA is increasing more rapidly than for any other cancer. Patients with metastatic melanoma have <5% survival after 5 years, and melanoma recently replaced leukemia as responsible for more lost hours in the work place. Currently there are no approved therapies for metastatic melanoma that achieve more than a 20% response rate. The University of Texas, M.D. Anderson Cancer Center currently manages the largest number of melanoma patients in the US. Together with Callisto Pharmaceuticals Inc., which develops small-molecule anticancer drugs, we propose to explore the potential development of a recently discovered novel antimelanoma drug, WP760. WP760, is a bis-intercalating DNA binding drug which has demonstrated remarkable selectivity towards melanoma cells, based on preliminary data from the NCI in vitro anti-tumor screen. Using the Compare Program, an algorithm that compares drug profiles, researchers at the NCI found WP760 to have a highly selective activity against melanoma that was distinctly unique and different from all of the 80,000 other cancer drugs to which it was compared. In this Phase I FLAIR STTR application, we propose to further evaluate WP760's potential as a drug to treat melanoma, with the intent of moving to clinical trials in melanoma and eventual commercialization. We propose optimization of production chemistry and formulation, performance of pharmocokinetics and toxicity in rodents, sensitivity of human melanoma vs. other tumors to growth inhibition by WP760 in vitro, and finally testing of efficacy in a human melanoma xenograft mouse model using systemic administration of WP760 to approach the human use. Successful completion of these objectives will then be followed by a Phase II STTR submission for final preclinical studies, leading to an IND application and clinical trial testing in humans. [unreadable] [unreadable] [unreadable]